Hematopoietic stem cells (HSC) have been the subject of intense investigation for many years. Until recently, the studies primarily examined populations of cells containing very few actual HSC. The rarity of these cells has made it difficult to obtain sufficient numbers of cells for study. Compounding this problem is the potential functional phenotypic diversity of the HSC populations. We have developed an HSC tracking assay which has allowed us to recover HSC following bone marrow transplantation into murine hosts which will allow us for the first time to study both the molecular and cellular characteristics of a potentially homogeneous population of HSC from adult bone marrow. The functional aspects include stem cell proliferation, differentiation, survival and homing in-vitro and in-vivo. The phenotypic characterization includes novel (as well as those suggested from population studies) cell surface markers as well as molecular regulatory molecules such as p27, a cyclin kinase inhibitor which could be responsible for HSC quiescence. In addition, accessory cell populations may very well play a regulatory role in HSC functions. It is our plan to be able to distinguish between HSC cellular divisions which result in maintenance of the HSC compartment, expansion of the compartment or depletion of the compartment. Finally, we will continue to examine developmentally immature HSC for engraftment potential gene expression and plasticity.